Uji Efektivitas Sediaan Gel Fraksi Etil Asetat Daun Jambu Biji (Psidium Guajava Linn) Terhadap Penyembuhan Luka Terbuka Pada Mencit (Mus Musculus)

Guava leaf has various benefits, one of them is accelerating the healing process of a wound. This study aims to formulate the ethyl acetate fraction into a gel form and test the effectiveness of gel formulation toward open wounds in 16 male mices (Mus musculus) which made excision 1 cm circular full thickness wound on the back of mice parallel with Os. vetebra. The ethyl acetate fraction of guava leaf has been made into concentrations of 5% and 7% with base gel used as negative control and Bioplacenton as positive control. The evaluation towards ethyl acetate fraction gels showed the gels have green-yellow color, guava odor, homogenous, relevant pH to the skin 6,31-6,51, and spread over 2,8-3 cm (stiff gel). The gels were applied onto the wounds twice a day for about 21 days. The observation was conducted every day towards the scab formation day, scab chipped day, and wound healing day. The data were analyzed statistically using one way ANOVA then continued with Tukey test. The average day for scab formation, scab chipped, and wound healing process, successively are in the negative control i.e. 6,50 ; 13,50 ; 20,25, then positive control of 3,75 ; 11,00 ; 17,25, for gel with 5% concentration, 3,75 ; 9,75 ; 16,50, and gel with 7% concentration, 4,50 ; 12,00 ; 18,25. The statistical result showed that the ethyl acetats fraction could accelerate the scab formation (p0,05). Gel concentration 5% accelerated faster in forming the scab, flaking off the scab, and healing the wound compared with the gel concentration of 7%

c-Myc regulates transcriptional pause release

Recruitment of the RNA polymerase II (Pol II) transcription initiation apparatus to promoters by specific DNA-binding transcription factors is well recognized as a key regulatory step in gene expression. We report here that promoter-proximal pausing is a general feature of transcription by Pol II in mammalian cells and thus an additional step where regulation of gene expression occurs. This suggests that some transcription factors recruit the transcription apparatus to promoters, whereas others effect promoter-proximal pause release. Indeed, we find that the transcription factor c-Myc, a key regulator of cellular proliferation, plays a major role in Pol II pause release rather than Pol II recruitment at its target genes. We discuss the implications of these results for the role of c-Myc amplification in human cancer.National Institutes of Health (U.S.) (Grant number RO1-HG002668)National Institutes of Health (U.S.) (Grant number RO1-GM34277)National Institutes of Health (U.S.) (Grant number RO1-CA133404)National Cancer Institute (U.S.) (Grant Number PO1- CA42063)National Cancer Institute (U.S.) Cancer Center Support Grant (Grant Number P30-CA14051)National Institutes of Health (U.S.) Postdoctoral Fellowship (5-F32-HD051190

Investigation of the correlation between odd oxygen and secondary organic aerosol in Mexico City and Houston

Many recent models underpredict secondary organic aerosol (SOA) particulate matter (PM) concentrations in polluted regions, indicating serious deficiencies in the models' chemical mechanisms and/or missing SOA precursors. Since tropospheric photochemical ozone production is much better understood, we investigate the correlation of odd-oxygen ([Ox]≡[O3]+[NO2]) [([O subscript x] ≡ [O subscript 3] + [NO subscript 2])] and the oxygenated component of organic aerosol (OOA), which is interpreted as a surrogate for SOA. OOA and Ox [O subscript x] measured in Mexico City in 2006 and Houston in 2000 were well correlated in air masses where both species were formed on similar timescales (less than 8 h) and not well correlated when their formation timescales or location differed greatly. When correlated, the ratio of these two species ranged from 30 μg [mu g] m−3/ppm [m superscript -3 / ppm] (STP) in Houston during time periods affected by large petrochemical plant emissions to as high as 160 μg [mu g] m−3/ppm [m superscript -3 / ppm] in Mexico City, where typical values were near 120 μg [mu g] m−3/ppm [m superscript -3 / ppm]. On several days in Mexico City, the [OOA]/[Ox] [[OOA] / O subscript x]] ratio decreased by a factor of ~2 between 08:00 and 13:00 local time. This decrease is only partially attributable to evaporation of the least oxidized and most volatile components of OOA; differences in the diurnal emission trends and timescales for photochemical processing of SOA precursors compared to ozone precursors also likely contribute to the observed decrease. The extent of OOA oxidation increased with photochemical aging. Calculations of the ratio of the SOA formation rate to the Ox [O subscript x] production rate using ambient VOC measurements and traditional laboratory SOA yields are lower than the observed [OOA]/[Ox] [[OOA] / O subscript x]] ratios by factors of 5 to 15, consistent with several other models' underestimates of SOA. Calculations of this ratio using emission factors for organic compounds from gasoline and diesel exhaust do not reproduce the observed ratio. Although not successful in reproducing the atmospheric observations presented, modeling P(SOA)/P(Ox) [P (SOA) / P (O subscript x)] can serve as a useful test of photochemical models using improved formulation mechanisms for SOA.National Science Foundation (U.S.) (Grant ATM-528227)National Science Foundation (U.S.) (Grant ATM-0528170)National Science Foundation (U.S.) (Grant ATM-0513116)National Science Foundation (U.S.) (Grant ATM-0449815)United States. Dept. of Energy. Office of Biological and Environmental Research. Atmospheric Science Program (Grant DE-FGO2-05ER63982)United States. Dept. of Energy. Office of Biological and Environmental Research. Atmospheric Science Program (Grant DEFGO2- 05ER63980)United States. Dept. of Energy. Office of Biological and Environmental Research. Atmospheric Science Program (Grant DE-FG02-08ER64627)United States. National Oceanic and Atmospheric Administration (Grant NA08OAR4310656

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results

Short RNAs Are Transcribed from Repressed Polycomb Target Genes and Interact with Polycomb Repressive Complex-2

Polycomb proteins maintain cell identity by repressing the expression of developmental regulators specific for other cell types. Polycomb repressive complex-2 (PRC2) catalyzes trimethylation of histone H3 lysine-27 (H3K27me3). Although repressed, PRC2 targets are generally associated with the transcriptional initiation marker H3K4me3, but the significance of this remains unclear. Here, we identify a class of short RNAs, ~50–200 nucleotides in length, transcribed from the 5′ end of polycomb target genes in primary T cells and embryonic stem cells. Short RNA transcription is associated with RNA polymerase II and H3K4me3, occurs in the absence of mRNA transcription, and is independent of polycomb activity. Short RNAs form stem-loop structures resembling PRC2 binding sites in Xist, interact with PRC2 through SUZ12, cause gene repression in cis, and are depleted from polycomb target genes activated during cell differentiation. We propose that short RNAs play a role in the association of PRC2 with its target genes.National Institutes of Health (U.S.) (Grant HG002668)National Institutes of Health (U.S.) (Grant NS055923

Tumor Suppressor RASSF1A Promoter: p53 Binding and Methylation

Oncogenes and tumor suppressors work in concert to regulate cell growth or death, which is a pair of antagonist factors for regulation of tumorigenesis. Here we show promoter characteristic of tumor suppressor RASSF1A, which revealed a p53 binding site in the distal and a GC-rich region in the proximal promoter region of RASSF1A, in despite of TATA box-less. The GC-rich region, which is ∼300 bp upstream from the RASSF1A ATG, showed the strongest promoter activity in an assay of RASSF1A-driving GFP expression. Methylation analysis of the CpG island showed that 78.57% of the GC sties were methylated in testis tumor samples compared with methylation-less in normal testis. Hypermethylation of the GC-rich region is associated with RASSF1A silencing in human testis tumors. In addition, electrophoretic mobility shift assay indicated that p53 protein bound to the RASSF1A promoter. Further chromatin immunoprecipitation confirmed p53 binding to the RASSF1A. Moreover, p53 binding to the promoter down-regulated RASSF1A expression. These results suggest that p53 protein specifically binds to the RASSF1A promoter and inhibits its expression. Our results provide new insight into the mechanism of action of tumor suppressors and may be a starting point for development of new approaches to cancer treatment

Randomized trials of artemisinin-piperaquine, dihydroartemisinin-piperaquine phosphate and artemether-lumefantrine for the treatment of multi-drug resistant falciparum malaria in Cambodia-Thailand border area

<p>Abstract</p> <p>Background</p> <p>Drug resistance of falciparum malaria is a global problem. Sulphadoxine/pyrimethamine-resistant and mefloquine-resistant strains of falciparum malaria have spread in Southeast Asia at lightning speed in 1980s-1990s, and the Cambodia-Thailand border is one of the malaria epidemic areas with the most severe forms of multi-drug resistant falciparum malaria.</p> <p>Methods</p> <p>Artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine phosphate (DHP) and artemether-lumefantrine (AL) were used to treat 110, 55 and 55 uncomplicated malaria patients, respectively. The total dosage for adults is 1,750 mg (four tablets, twice over 24 hours) of AP, 2,880 mg (eight tablets, four times over two days) of DHP, and 3,360 mg (24 tablets, six times over three days) of AL. The 28-day cure rate, parasite clearance time, fever clearance time, and drug tolerance of patients to the three drugs were compared. All of the above methods were consistent with the current national guidelines.</p> <p>Results</p> <p>The mean parasite clearance time was similar in all three groups (66.7 ± 21.9 hrs, 65.6 ± 27.3 hrs, 65.3 ± 22.5 hrs in AP, DHP and AL groups, respectively), and there was no remarkable difference between them; the fever clearance time was also similar (31.6 ± 17.7 hrs, 34.6 ± 21.8 hrs and 36.9 ± 15.4 hrs, respectively). After following up for 28-days, the cure rate was 95.1%(97/102), 98.2%(54/55) and 82.4%(42/51); and the recrudescence cases was 4.9%(5/102), 1.8%(1/55) and 17.6%(9/51), respectively. Therefore, the statistical data showed that 28-day cure rate in AP and DHP groups was superior to AL group obviously.</p> <p>The patients had good tolerance to all the three drugs, and some side effects (anoxia, nausea, vomiting, headache and dizziness) could be found in every group and they were self-limited; patients in control groups also had good tolerance to DHP and AL, there was no remarkable difference in the three groups.</p> <p>Conclusions</p> <p>AP, DHP and AL all remained efficacious treatments for the treatment of falciparum malaria in Cambodia-Thailand border area. However, in this particular setting, the AP regimen turned out to be favourable in terms of efficacy and effectiveness, simplicity of administration, cost and compliance.</p> <p>Trial Registration</p> <p>The trial was registered at <it>Chinese Clinical Trial Register </it>under identifier 2005L01041.</p

Statistical Use of Argonaute Expression and RISC Assembly in microRNA Target Identification

MicroRNAs (miRNAs) posttranscriptionally regulate targeted messenger RNAs (mRNAs) by inducing cleavage or otherwise repressing their translation. We address the problem of detecting m/miRNA targeting relationships in homo sapiens from microarray data by developing statistical models that are motivated by the biological mechanisms used by miRNAs. The focus of our modeling is the construction, activity, and mediation of RNA-induced silencing complexes (RISCs) competent for targeted mRNA cleavage. We demonstrate that regression models accommodating RISC abundance and controlling for other mediating factors fit the expression profiles of known target pairs substantially better than models based on m/miRNA expressions alone, and lead to verifications of computational target pair predictions that are more sensitive than those based on marginal expression levels. Because our models are fully independent of exogenous results from sequence-based computational methods, they are appropriate for use as either a primary or secondary source of information regarding m/miRNA target pair relationships, especially in conjunction with high-throughput expression studies